論文 - 詳細
| RRC ID | 34852 |
|---|---|
| 著者 | Huang C, Harada Y, Hosomi A, Masahara-Negishi Y, Seino J, Fujihira H, Funakoshi Y, Suzuki T, Dohmae N, Suzuki T. |
| タイトル | Endo-β-N-acetylglucosaminidase forms N-GlcNAc protein aggregates during ER-associated degradation in Ngly1-defective cells. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
The cytoplasmic peptide:N-glycanase (PNGase; Ngly1 in mice) is a deglycosylating enzyme involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) process. The precise role of Ngly1 in the ERAD process, however, remains unclear in mammals. The findings reported herein, using mouse embryonic fibroblast (MEF) cells, that the ablation of Ngly1 causes dysregulation of the ERAD process. Interestingly, not only delayed degradation but also the deglycosylation of a misfolded glycoprotein was observed in Ngly1(-/-) MEF cells. The unconventional deglycosylation reaction was found to be catalyzed by the cytosolic endo-β-N-acetylglucosaminidase (ENGase), generating aggregation-prone N-GlcNAc proteins. The ERAD dysregulation in cells lacking Ngly1 was restored by the additional knockout of ENGase gene. Thus, our study underscores the functional importance of Ngly1 in the ERAD process and provides a potential mechanism underlying the phenotypic consequences of a newly emerging genetic disorder caused by mutation of the human NGLY1 gene. |
| 巻・号 | 112(5) |
| ページ | 1398-403 |
| 公開日 | 2015-2-3 |
| DOI | 10.1073/pnas.1414593112 |
| PII | 1414593112 |
| PMID | 25605922 |
| PMC | PMC4321286 |
| MeSH | Acetylglucosamine / metabolism* Animals Cells, Cultured Endoplasmic Reticulum / metabolism* Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / metabolism* Mice Mutation Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / genetics Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / metabolism* Radioimmunoprecipitation Assay |
| IF | 9.412 |
| 引用数 | 46 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pEF/RTAdelta/myc/ER (RDB13411) pEF/RTAdelta/V5-myc/ER (RDB13412) pEF/RTAdeltaN10Q/V5-myc/ER (RDB13413) pEF/RTAdeltaN236Q/V5-myc/ER (RDB13414) pEF/RTAdeltaN10QN236Q/V5-myc/ER (RDB13415) pEF/RTAdeltaN10DN236Q/V5-myc/ER (RDB13416) pcDNA3.1/ENGase/FLAG-His (RDB13417). |